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Berberine Suppresses TNF-α-induced MMP-9 and Cell Invasion through Inhibition of AP-1 Activity in MDA-MB-231 Human Breast Cancer Cells

1
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea
2
Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, South Korea
*
Authors to whom correspondence should be addressed.
Molecules 2008, 13(12), 2975-2985; https://doi.org/10.3390/molecules13122975
Received: 10 November 2008 / Revised: 25 November 2008 / Accepted: 26 November 2008 / Published: 3 December 2008
Invasion of cancer cell induced by matrix metalloproteinase-9 (MMP-9) is one of pivotal steps in cancer metastasis. Herein, we investigated how cell invasion was regulated by berberine (BBR), an isoquinoline derivative alkaloid compound, in MDA-MB-231 human breast cancer cells. The basal level of MMP-9 activity and expression was dose-dependently increased by TNF-α, while TNF-a-induced MMP-9 gelatinase activity and expression was decreased by BBR. To investigate regulatory mechanism of TNF-α-induced MMP-9 expression, we pretreated cells with UO126 (MEK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor), respectively. Interestingly, TNF-α-induced MMP-9 activity and expression was decreased by UO126 and SB203580, but not by SP600125. Therefore, we further examined the effects of BBR on TNF-α-induced AP-1 DNA binding activity which is a downstream target of ERK and p38. Our data showed that TNF-α-induced AP-1 DNA binding activity was inhibited by BBR. Finally, we investigated the effect of BBR on TNF-α-induced cell invasion. TNF-α-induced cell invasion was significantly decreased by BBR treatment. Taken together, we suggest that TNF-α-induced MMP-9 expression and cell invasion are decreased by BBR through the suppression of AP-1 DNA binding activity in MDA-MB-231 human breast cancer cells. View Full-Text
Keywords: Berberine; AP-1; MMP-9; Cell invasion Berberine; AP-1; MMP-9; Cell invasion
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Kim, S.; Choi, J.H.; Kim, J.B.; Nam, S.J.; Yang, J.-H.; Kim, J.-H.; Lee, J.E. Berberine Suppresses TNF-α-induced MMP-9 and Cell Invasion through Inhibition of AP-1 Activity in MDA-MB-231 Human Breast Cancer Cells. Molecules 2008, 13, 2975-2985.

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